TW200303219A - Tablets having improved tabletting characteristics and process for producing the same - Google Patents

Abstract

It is intended to provide tablets which have a favorable texture in taking and excellent tabletting characteristics, abrasion resistance and mechanical strength. Tablets which are produced by blending a powdery or granular mixture comprising (1) an effective amount of a pharmacologically active substance and (2) 50% by weight or more of a water-soluble filler with (3) a tabletting characteristic improving agent containing moisture at least in an amount corresponding to the equilibrated moisture content at 25 DEG C under a humidity of 12% and having an average grain size of 100 μ m or less, at a ratio of 1 to 50 % by weight based on the above mixture, and then tabletting the resultant mixture.

Description

200303219 (1) 发明. Description of the invention [Technical field to which the invention belongs] The present invention relates to a tablet compression method, in particular to an orally disintegrating tablet and [prior art] The intraoral disintegrating tablet is due to the advanced age in the oral cavity Those who are not easy to take tablets and also easily disintegrate tablets are those who have excellent feeling of taking such as rough feeling due to disintegration in the oral cavity. Therefore, the sugar, sugar alcohol and the like are water-soluble excipients. For example, in W093 / 1 2769, the solution of a pharmacologically active ingredient is freeze-dried, air-dried or dried. In addition, its intraoral disintegrating tablet lacks organic PTP packaging, and the disintegration is unavoidable when it is taken out of Japanese Unexamined Patent Publication No. 5-271054, orally, a disintegrating agent for wet tablets on the surface of sugars and sugar particles. The disintegrating agent is on the particle surface, and the mixture before adjusting the moisture content of the mixture is adjusted to a uniform wet mixture with extremely low water content. It is filled in the object and remains in the tablet machine, and the improved tablet and its manufacturing方 其 Manufacture method. Disintegrates quickly, so even young children, taking tablets. The oral cavity is expected to develop a disintegrated taste. Usually, increasing the proportion of disintegrating tablets can increase the disintegrating tablets and the publication No. W094 / 12 1 42 or the suspension is filled in a formed bag and dried under reduced pressure. The strength of the disintegrating tablet in the oral cavity is such that the disintegrating tablet is damaged by the tablet. It was revealed that a mixture containing water having a pharmacologically active degree of moistening was added to the sugar before the tableting, and the whole sugar was added to make it. In addition, it is extremely difficult to make a spindle. In addition, the fluidity of the spindle should be avoided. When the wet mixture is filled, the filling of the wet mixture will be uneven. -5- (2) (2) 200303219 The method of this publication requires that the tablets be dried after tabletting as a necessary step. In W093 / 203 80, a disintegrating tablet containing sugar alcohol having low moldability and sugar alcohol having moldability is disclosed. In addition, when the sugar alcohol content is high, there are disadvantages such as hindering tableting of coatings and the like. Therefore, the disintegrating tablets of this publication do not have a satisfactory degree of tabletability. The use of sugars, sugar alcohols, and other water-soluble excipients lacking moldability and increasing their content ratio can improve the tablet's feeling of taking. When the content ratio is high, the lack of tabletability is as described above. Tablets with good tablet feel and excellent tabletability have not been developed. Therefore, it has been desired to develop a tablet that can solve both the problem of improving the feeling of taking a tablet and improving the tabletability, and that is simple and has high productivity. [Summary of the Invention] The present invention aims to provide a tablet having a good feeling of taking a tablet and excellent tableting properties, abrasion resistance, and mechanical strength. The present invention aims to provide an orally disintegrating tablet which is easy to be tableted, has sufficient tabletability, abrasion resistance, and mechanical strength, and is rapidly disintegrated in the oral cavity. As a result of the intent of the present inventors to solve the above-mentioned problems, when a large amount of water-soluble excipients are added to a pharmaceutical preparation, when a specific ratio of a tableting improver having a specific amount of water is added, the problem can be solved. . The present invention has been completed based on such knowledge. 1. A tablet, characterized by powder or granules containing (1) an effective amount of pharmacological activity-6- (3) (3) 200303219 substance and (2) 50% by weight or more of water-soluble excipients In the mixture, (3) a tabletability improver having an equilibrium moisture of a temperature of 25 ° C and a humidity of 12% or more and an average particle diameter of 100 #m or less, and for the mixture, 1 to 50% by weight is added and tabletted. 2. —A method for manufacturing a tablet, characterized in that in a powdery or granular mixture containing (1) an effective amount of a pharmacologically active substance and (2) 50% by weight or more of a water-soluble excipient, ( 3) A tableting improver having a moisture of more than equilibrium moisture at a temperature of 25 ° C and a humidity of 12%, and an average particle diameter of 1000 // m or less, and 1 to 50% by weight of the mixture. Proportions added and compressed. 3. —Intra-oral disintegrating tablet, characterized in that (3) a powdery or granular mixture containing (1) an effective amount of a pharmacologically active substance and (2) 50% by weight or more of a water-soluble excipient, (3 ) A tableting improver with a moisture content above the equilibrium moisture of 25 ° C and a humidity of 12% and an average particle size of 1 0 0 // m or less, for the mixture at 1 to 50% by weight Proportionally added and compressed. 4. A method for manufacturing an orally disintegrating tablet, characterized in that it is mixed in a powdery or granular form containing (1) an effective amount of a pharmacologically active substance and (2) 50% by weight or more of a water-soluble excipient, (3) A tableting improver having a moisture content of 25 ° C or more and a moisture balance of 12% or more, and an average particle size of 100 # m or less, and 1 to 50% by weight of the mixture. Proportions added and compressed. The best form to implement the present invention-7- (4) (4) 200303219 The tablet of the present invention is a powdery or granular mixture containing a pharmacologically active substance and a water-soluble excipient, and a specific tabletting property is added Improver and made by tabletting. First, a description is given of a powdery or granular mixture. Pharmacologically active substances are widely known. Examples of such pharmacological substances include preparations for respirators, preparations for digestive organs, preparations for circulatory organs, preparations for central nerves, preparations for peripheral nerves, preparations for antibiotics, chemotherapeutics, antitumor agents, platelet coagulation inhibitors, and antibacterial agents. General pharmacological substances added to various preparations of allergens and vitamins. Specific examples thereof are, for example, theophylline, cilostaz 〇1, Rrepafloxacia, Carteol 010, procaterol, ribapi (Rebaniipid), aripiprazol, etc. And powdery or granular mixtures can be added with effective amounts of pharmacologically active substances. Water-soluble excipients are widely known, and examples thereof include sugars, sugar alcohols, water-soluble polymer substances, and agar gum. Specific examples of the sugar include monosaccharides such as glucose, fructose, and sugar, and oligosaccharides such as maltose, lactose, sucrose, and trehalose. Specific examples of the sugar alcohol 'include mannitol, sorbitol, maltitol, erythritol, and xylitol. Specific examples of the soluble polymer substance 'include polyethylene glycol [microgol (trade name)], and polypropylene glycol. These water-soluble excipients can be used singly or in combination of two or more kinds. Among the water-soluble excipients, sugar alcohols are most preferred. -8- (5) (5) 200303219 The content of the water-soluble ingredient in the powdery or granular mixture is generally 50% by weight or more, preferably 60 to 90% by weight, and most preferably 70% to 99% by weight. The powdery or granular mixture may suitably contain other additives in addition to the pharmacologically active substance and the water-soluble excipient, if necessary. Examples of such additives include spices and sweeteners. Examples of the fragrance system include clear extract, clear oil, vanilla oil, peppermint oil, vanilla fragrance, lemon oil, 1-menthol, and the like. Examples of sweeteners include aspartame, sodium saccharin, sweet tea, licorice, glycerin, honey, water mussel and the like. These additives may be used alone or in combination of two or more. Mixtures containing pharmacological substances and water-soluble excipients, preferably granules. The granular mixture is produced by, for example, mixing a pharmacologically active substance and a water-soluble excipient d and granulating the obtained powdery mixture. The granulation system can be performed by a known method such as a wet method and a dry method. When manufacturing the tablet of the present invention, a tableting improver having a moisture content of a balance moisture of 25 ° C or higher and a humidity of 12% or higher can be used. Examples of the tabletability improving agent having a moisture balance of 2 5 C and a humidity of 12% or more and an average particle diameter of 100 # m or less include starch, cellulose, and high Molecular substances have this point. Starch types such as wheat starch, rice starch, corn starch, maltese starch, dextrin, α-starch, partially α-starch, hydroxypropyl splash powder, cumyl methyl powder, α-cyclodextrin '/ 3 -Cyclodextrin, 1,3-/ 3 -glucozide, etc.-9- (6) (6) 200303219 Cellulose systems include crystalline cellulose, hydroxypropyl cellulose, and low-substituted hydroxypropyl fibers Cellulose, hydroxypropyl methyl cellulose, carboxymethyl, residual methyl cellulose calcium, sodium carboxymethyl cellulose, croscarmellose sodium and the like. Examples of the polymer substance include synthetic polymer substances such as polyvinyl alkanone and polyvinyl alcohol, and natural polymer substances such as agar gelatin and gelatin. Among these tabletting improvers, the most preferable is a tabletting improver. Corn starch, potato starch, crystalline cellulose, low-substitution hydroxypropyl cellulose, polyethylene ratio alkanone, etc. The equilibrium moisture at a temperature of 25 ° C and a humidity of 12% varies depending on the type of tableting improver. Temperature 25 ° C and humidity 12%. For example, the balanced moisture is about 5.3% of corn starch. 'Potato source flour is about 15%, some alpha starch is 4%, and crystalline fiber is about 2.3 ~ 2.5%. The substituted hydroxypropyl cellulose is about 3.0 to 3.1%, and the polyethylene ratio is about 3.5 to 3.8%. In the present invention, the equilibrium moisture at a temperature of 25 ° C and a humidity of 12% is the moisture in which each compound is placed in a desiccator with a saturated aqueous solution of lithium chloride, and it is left at 25 ° C for 48 hours. The particle size is measured using a volumetric card moisture meter (trade name: KF-〇6, manufactured by Mitsubishi Chemical Co., Ltd.), for example, corn starch is about 2 ~ 3 2 // m, potato starch System is about 7 〇 ～ 9 0 // m, partly α 丨 Dianfen system is about 7 0 # m (average straight), knot -10- (7) (7) 200303219 crystal fiber system is about 1 7 ～ 40 // m Low-substituted hydroxypropyl cellulose is about 25 ~ 50 // m, and polyethylene ratio is 30 ~ 75 / zm. These tableting improvers can be used singly or in combination of two or more. The tableting improvers are usually added in a powder or granular form containing a pharmacologically active substance and a water-soluble excipient. % Or more, preferably 2 to 50% by weight, and more preferably 5 to 20% by weight. The tablets of the present invention are added to a mixture containing a pharmacologically active substance and a water-soluble excipient, and a specific amount of the specific compression improving agent is added, and the additive is then manufactured by a tablet manufacturer. When tableting, a known tableting method can be widely used. Since the device for manufacturing the tablet is a conventional device generally used for preparations of oral preparations, it is not necessary to use a special manufacturing device. The tabletability is improved by the addition of the specific tabletability improver. Therefore, when the tablet is formed, there are no problems such as hindering of tableting, such as covering, and insufficient tablet hardness. As a result, the tablet of the present invention can be manufactured without using a special manufacturing device, and using a general tablet manufacturing device. The tablet of the present invention has sufficient abrasion resistance and mechanical strength, and therefore, it does not cause damage at the time of packaging operation and unsealing of PTP. The tablets of the present invention are intended to be taken by young children and the elderly due to rapid disintegration or dissolution in the oral cavity. [Embodiment] Examples -11-(8) (8) 200303219 Hereinafter, the present invention will be explained more clearly with examples and comparative examples. The details of the tableting improver used below are as follows. Moisture content in various tableting improvers is measured using a volumetric card moisture meter. 0 Corn starch: made by Japan Food Processing Co., Ltd., particle size 2 ~ 3 2 // m, temperature 2 5 ° C , Humidity 12% after storage for 4 8 hours, equilibrium moisture 5.3% potato: made by Nitto Chemical Co., Ltd., particle diameter 70 ~ 90 // m, stored at 25 ° C, humidity 2% 48 After 1 hour, the equilibrium moisture is 1.5%. A Sailu PH — F20 (trade name): crystalline cellulose, manufactured by Asahi Kasei Corporation, average particle diameter 1 7 // m, at temperature 2 5 ° C, humidity 1 2% of the equilibrium moisture after 8 hours of 2.5% Asailu PH — 301 (trade name): crystalline cellulose, manufactured by Asahi Kasei Corporation, average particle diameter 4 0 // m, at temperature 2 5 ° C, Humidity: 12% Equilibrium moisture after storage for 4 8 hours: 2.3% LH-31: Low-substitution hydroxypropyl cellulose, manufactured by Shin-Etsu Chemical Co., Ltd., with an average particle diameter of 2 5 // m. Temperature 2 5 ° C, humidity 12%. Equilibrium moisture after storage for 4 to 8 hours 3.1% LH-1 1: low substitution hydroxyl Based on cellulose, manufactured by Shin-Etsu Chemical Co., Ltd., with an average particle diameter of 50 0 // m, and a temperature of 25 ° C and a humidity of 12% for 48 hours, the equilibrium moisture is 3.0% PVP (XL — 10): Polypropyl than each alkanone made by Japan ISP (Co., Ltd.), average particle diameter 30 millimeters, at temperature 2 5 ° C, humidity] 2% -12- 200303219 〇) After storage for 4 8 hours Equilibrium moisture: 5.8% PVP (XL): made of polypropyl acetone, manufactured by Japan ISP (Co., Ltd.), average particle diameter 7 5 // m, stored at temperature 2 5 ° C, humidity 12%, stored for 4 8 hours Equilibrium moisture at the rear 3.5% Fuki Carin SG (trade name): Calcium phosphate, manufactured by Fuji Chemical Industry Co., Ltd., average particle diameter 1 13 // m, stored at 25 ° C and 12% humidity After 48 hours, the equilibrium moisture content was 0.9%. Car B was processed (heated to 80 ° C. for more than 3 hours in a vacuum) and the various tableting improvers were prepared to obtain adjusted product A. In addition, a humidification treatment (stored at a temperature of 25 ° C and a humidity of 60% for 24 hours or more) of these various tabletability improving agents was used to prepare an adjusted product D. The adjustment product A and the adjustment product D were mixed to obtain an adjustment product B and an adjustment product c. The moisture content of these adjusted products is shown in Table 1.

• 13- (10) 200303219 Table 1 (3) Adjusted water content (%) Modifier A Modifier B Modifier C Modifier D Corn starch 3.0 6.1 9.1 13.5 Potato starch 0.7 9.2 Asailu PH- F20 1.7 2.7 6.2 8.3 Asailu PH- 301 1.2 6.7 LH- 3 1 1.2 4.0 7.9 10.5 LH- 1 1 0.8 6.5 P VP (XL-10) 1.7 18.7 PVP (XL) 0.9 6.1 11.3 18.5 Fuki Carin SG (Commodity First name) 0.6 2.5

Snoring test 1 Prepare sugar alcohol-based particles (prescriptions 1 to 3) shown in Table 2 below. The granulation of each pellet was carried out by a stirring flow granulation method using a Marubeni Precus MP-01 (trade name) (produced by P 0 W R E X). -14- (11) 200303219 Table 2 Formula 1 Formula 2 Formula 3 Erythritol (mg) 147 Mannitol (mg) 147 Xylitol (mg) 147 HPC- L (mg) 3 3 3 Total (mg) 1 50 1 50 1 50 HPC-L: Japan Cao Da (Co., Ltd.) made the particle size of Formula 1 1 3 3 // m, the particle size of Formula 2 was 102 / zm, and the particle size of Formula 3 was 299 // m . For the granules of prescriptions 1 to 3, add 0.5% by weight of lubricant (magnesium stearate, manufactured by Taiping Chemical Industry Co., Ltd.), and use a tableting machine (12HUK, manufactured by Kikusui Manufacturing Co., Ltd.) Press the ingot to press 1 0 0 0 0 g g. When punching, use a pestle rod with a diameter of 8 mm and a clearance angle of R. Investigate the injectability of the ingots (whether there is a covering, increased decompression, or increased noise). When the mixture to which magnesium stearate was added was granulated into granules of Formula 1, the generation of the covering was confirmed. When the mixture containing magnesium stearate was granulated into the granules of Formula 2 or Formula 3, it was confirmed that the decompression increased and the noise increased. From these results, it has been found that the spindle properties of any mixture are not good. For granules of prescriptions 1 to 3, adjusters A to D 10 are added at 10% by weight. In addition, a lubricant (magnesium stearate, manufactured by Taiping Chemical Industry Co., Ltd.) was added to the granular mixture after the adjustment products A to D were added by 0.5% by weight. The obtained mixture was beaten with a tableting machine (made by 12HUK 'Kikusui Seisakusho Co., Ltd. (15-200303219 (12) Co., Ltd.)), and pressed at a rate of 1,000 kg. When punching, use a pestle rod with a diameter of 8 mm and a clearance angle of R. Investigate the injectability of the ingots (whether there is a covering, increased decompression, or increased noise). Regarding the granules of prescriptions 1 to 3, compared with the 0.5% by weight mixture of added lubricant (magnesium stearate, manufactured by Taiping Chemical Industry Co., Ltd.), it is impossible to fully identify the impediment of the tableting (whether there is a covering or an increase in decompression). Or increase in noise) is X when it is improved or deteriorated, it can be considered that the improvement of swirling resistance (whether a cover is generated, decompression increase or noise increase) or there is almost no spindle resistance is 0 '. If it is obstructed (whether a cover is generated, the pressure is reduced, or the noise is increased), it can be judged as ◎. The results are shown in Tables 3 and 4. (13) 200303219 Table 3

Improver for prescription 3 (3) Modified product of corn starch AXB 〇C ◎ D ◎ Potato starch AXD 〇 Asailu AX PH- F20 B ◎ D ◎ Asailu AX PH- 301 D ◎ LH- 3 1 AXB ◎ D ◎ LH- 1 1 AXD ◎ P VP (XL-10) AXD ◎ PVP (XL) AXB 〇C ◎ D ◎ Fuki Carin SGAX (brand name) DX

-17- (14) 200303219 Table 4

(3) Improver Modifiers Prescriptions 1 Prescriptions 2 Tableting properties Tableting properties King rice starch A X X B ο 〇 C 〇 ◎ D ◎ ◎ PVP (XL) A X X B 〇 〇 D ◎ ◎ Fuki Carin A X X D X X

Although it contains the average water content after 48 hours of storage at a temperature of 25 ° C and a humidity of 12%, the Fukikalin SG (trade name) with an average particle diameter of more than 100 / zm cannot improve the tableting properties when ingoting. Tables 3 and 4 show that the tableting test 2 prepared the granules using sugar alcohol as a base in the following manner. The granulation of the granules was performed by a stirring flow granulation method using a Marubeni Precus Mp — 〇1 (manufactured by P W RW E X Corporation). Granule formula 4: • 18- (15) (15) 200303219 Erythritol 1 1 7 weight part Corn flour 3 0 weight part HPC- L 3 weight part The particle size of prescription 4 is 16 / m. For the granules of Formula 4, 0.5% by weight of lubricant (magnesium stearate, manufactured by Taiping Chemical Industry Co., Ltd.) was added, and a tableting machine (12HUK, manufactured by Kikusui Manufacturing Co., Ltd.) was used for tabletting. 1 0 0 0 kg ingot. The ingot-making system uses a rod with a diameter of 8 mm and a clearance angle of R. Investigate the injectability of the ingots (whether there is a covering, increased decompression, or increased noise). When a mixture of magnesium stearate was added to the granulated tablets of the prescription, generation of a covering was confirmed. For the granules of Formula 4, corn starch (adjustments A to D) was added at 10% by weight. To the granulated mixture after the adjustments A to D were added, a lubricant (magnesium stearate, manufactured by Taiping Chemical Industry Co., Ltd.) was added in an amount of 0.5% by weight. The obtained mixture was pressed with a tableting machine U2HUK and Kikusui Manufacturing Co., Ltd. to produce a 1000 kg tablet. The ingots are punched with a diameter of Smm and a clearance angle of R. Investigate the same method as ingot injecting test 1 and determine the injectability (increase of depressurization or increase of noise) when injecting industy ° Determination of the mixture of "adjustment A" added to the granules of prescription 4 X, the determination of the mixture of the adjustment product B added to the granule of prescription 4 is the determination of the foot system of the mixture of the whole stomach 1 C added to the granule of the prescription 4, and the addition of the mixture of adjustment D Judgment ◎ ° -19- (16) (16) 200303219 Ingot Test 3 For the pellets (inject test) of Formula 4, corn starch (adjustment) was added at 5% or 10% by weight. To the granulated mixture after the adjustment product D was added, a lubricant (magnesium stearate, manufactured by Taiping Chemical Industry Co., Ltd.) was added at 0.5% by weight. The obtained mixture was pressed with a tableting machine (12HUK, manufactured by Kikusui Seisakusho Co., Ltd.) at a rate of 1 000 kg. The ingot was punched with a pestle rod having a diameter of 8 mm and a clearance angle of R. In comparison, even if corn starch (adjustment D) was not added, the same known tableting pressure was used to beat 1000 kg of tableting. The average weight (mg), average hardness (kp), and average thickness (mm) of each of the obtained tablets were measured. The average weight (mg) is the average weight of 10 tablets. The average hardness (k p) was measured using a tablet hardness tester (model 6 d, manufactured by Xueluo Niklu), and the average hardness was measured for 5 tablets. The average thickness (mm) was measured using a thickness gauge (model g, manufactured by PEACOCK), and the thickness of 5 tablets was averaged. Each of the obtained tablets was subjected to a disintegration test. The disintegration test is performed using a disintegration tester (model NF-2F, manufactured by Toyama Industry Co., Ltd.) 'in accordance with the Japan Pharmacy (14 Bureau amendments). The disintegration time (seconds) in the oral cavity of each tablet is the average of 2 tablets. Investigate the injectability (injection of cover) during injecting by the same method and judgement as in injecting test 1. -20- (17) 200303219 The results are shown in Table 5. Table 5 (3) Additive content of 0% 5% 10% Ingot pressing pressure (kg) 1000 1000 1000 Average weight (mg) 150.4 158.2 168.9 Average hardness (kp) 3.5 5.3 5.8 Average thickness (mm) 2.96 3.06 3.22 Collapse Bad time (seconds) 22 ～ 28 20 ～ 30 23 ～ 41 Oral disintegration time (seconds) 18 19 19 Cover generation > 6τΤ. Μ No addition of corn starch (adjustment D) can confirm the production of the cover However, by adding 5% by weight of corn starch (adjustment D), the production of coverings can be completely prevented. In addition, an increase in the hardness of the tablet was confirmed by the amount of corn starch added. Regarding disintegration, when corn starch (adjustment D) is not added, it is about the same as when corn starch (adjustment D) is added at 5% by weight. The disintegration was slightly reduced by the disintegration test of 10% by weight of corn starch (adjustment D), and the difference was not confirmed when no corn flour (adjustment D) and 5% by weight were added during oral disintegration. . Tableting test 4 Tablets 21-(18) 200303219 were manufactured in the same manner as in tableting test 1 in the following Table 6 using the method of tableting test 3 to determine the average weight of each tablet ( mg), average thickness (mm), average hardness (kp), and solution time (seconds). The abrasion degree (%) is the abrasion degree of a tablet (20 pieces) after a rotation speed of 25 rpm and a rotation speed of 25 rpm using a friction tester (model TF T-120, manufactured by Toyama Industry Co., Ltd.). In addition, the same method as that of the ingot test 1 was investigated.

Pastilleness (whether the cover is produced). The result shows% _ 6

-22- (19) 200303219 Table 6 Prescription 5 Prescription 6 Prescription 7 aripiprazol (mg) 15 15 15 Erythritol (mg) 102 1 02 102 Corn starch (mg) 3 0 3 0 30 HPC- L 3 3 3 (3 ) Improver Corn starch (mg) 15 PCS (mg) 7.5 PVP (XL) (mg) 7.5 Magnesium stearate (mg) 0.8 0.8 0.8 Total (mg) 165.8 15 8.3 158.3 Tablet pressure (kg) 600 600 600 Average Weight (mg) 166.3 157.8 157.4 Average thickness (mm) 3.25 3.14 3.18 Average hardness (kp) 3.3 3.4 3.7 Crash time (water) (minutes) 24 ～ 29 25 ～ 30 1 5 ～ 20 Good tabletability Good good corn starch Water content: 13.5% PCS water content: 1 2. .3% PVP (XL) water content: 1 8.5% -23- (20) (20) 200303219 Ingot test 5 Use the following table 7 for 'use and ingot Tablets were produced in the same manner as in Test 1. The average weight (mg), average thickness (mm), average hardness (kp), and disintegration time (seconds) of each of the tablets obtained were measured in the same manner as in the tableting test 3. The degree of abrasion (%) was measured by the same method as in the ingot test 4. In addition, the same method as that of the ingot test 1 and the determination of the injectability (whether a cover was generated) during ingot ingotting were investigated. The results are shown in Table 7. -24 · (21) (21) 200303219 Table 7 Formula 8 Formula 9 Formula 10 Formula 11 Pharmacologically active substance A (mg) 15 15 Pharmacologically active substance B (mg) 15 15 Erythritol (mg) 102 102 102 102 Corn starch (mg) 30 30 30 30 HPC-L (mg) 3 3 3 3 (3) Improver corn starch (mg) 15 15 PVP (XL) (mg) 7.5 7.5 magnesium stearate (mg) 0.8 0.8 0.8 0.8 Total (Mg) 165.8 158.3 158.3 158.3 Ingot pressure (kg) 800 800 600 600 Average weight (mg) 165.5 158.4 168.1 157.6 Average thickness (mm) 3.18 3.14 3.33 3.23 Average hardness (kp) 3.7 3.9 3.7 3.4 Crash time (water) (Minutes) 24 ～ 35 21 ～ 23 35 ～ 40 25 ～ 28 Abrasion (%) 0.7 0.3 1.4 1.0 Good tabletability Good Good Moisture of corn starch: 1 3.5% Moisture of PVP (XL): 18.5% -25- (22) (22) 200303219 About the pharmacologically active substance a of Table 7 i- [3-{4 ~ (3 ~ chlorobenzene) — 1- than Qinyl 丨 propyl 5-methoxy 3 , 4 Dihydrogen ~ 2 (1 H) -Quulin monomethane sulfonate. In addition, the pharmacologically active substance B is (5 R) ~ 2-[1 — {2 —chloro ~ $ one (一 — than each end) benzene 醯 丨-2, 3, 4, 5-tetrahydro ~ 1H- b Benzylidene-5-yl] -N-isopropylacetamido. Tableting test 6 Tablets were produced in the same manner as in the tableting test 1 using the method shown in Table 8 below. Using the phase R method with the fine test § 3, the average weight (mg), average thickness (mm), average hardness (kp), and disintegration time (seconds) of each tablet produced were measured. In addition, the same method as that of the ingot test 1 and the determination of the injectability (whether a cover was generated) during ingot ingotting were investigated. The results are shown in Table 8. -26- (23) 200303219 Table 8 Prescription 12 Prescription 13 Cilostazol 11 (cilostazol) (mg) 50 50 Erythritol (mg) 146 48 HPC- L 4 2 (3) Improver PVP (XL) ( mg) 10 5 Magnesium stearate (mg) 1.1 0.5 Total (mg) 211.1 105.5 Shape of pestle rod diameter 10.5mm clearance angle R diameter 7mm, sugar-coated R (5.5R) tablet pressure (kg) 600 300 average weight (mg ) 212.9 105.3 Average thickness (mm) 3.16 3.58 Average hardness (kp) 4.3 5.6 Crash time (water) (minutes) 15 ～ 20 20 ～ 25 Good tabletability Good moisture content of PVP (XL): 1 8.5%

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Claims (1)

(1) (1) 200303219, patent application scope 1. A tablet 'characterized by a powder or containing a (n) effective amount of a pharmacologically active substance and (2) a water-soluble excipient of 50% by weight or more In the granular mixture, (3) a tableting improver having a moisture content of 2VC or higher and a moisture balance of 12% or more and an average particle diameter of 100 / m or less, and 1 to 50 for the mixture It is added in the proportion of% by weight and tabletted. 2. A method for manufacturing a tablet, characterized in that (3) a powdery or granular mixture containing (1) an effective amount of a pharmacologically active substance and (2) 50% by weight or more of a water-soluble excipient, ) A tabletting improver with a moisture content of 25 ° C or more and an equilibrium moisture content of I2% and an average particle size of 1 0 0 // m or less, added to the mixture in a proportion of 1 to 50% by weight And tablet player-28-